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Mitomycin C, vinblastine and cisplatin combination chemotherapy in the treatment of advanced non-small cell lung cancer
S36
disease. There was partial remission, six with doxorubicin, seven with epirubicin (one death in each group), and no response in five (doxorubicin; two deaths) and seven (epirubicin; five deaths). Toxicity was greater during and after cyclophosphamide and etoposide than during and after vincristine with either doxorubicin or epirubicin. Substitution of epirubicin for doxorubicin appeared not to offer any advantage in reduction in toxicity in the treatment of small cell lung cancer as used in this series. The low complete remission rate, the relatively high proportion of non-responders and the low incidence of serious leucopenia indicates that the therapeutic regimen used was sub-optimal. It is suggested that this may bc because the treatment schedule was every four weeks instead of the more usual three-weekly treatments and the lack of cardiac toxicity may be because no patients received more than 200 mg/m2. It is concluded therefore that it would be worth including epirubicin into a more intensive treatment protocol, using a higher total dose and scheduling. the treatment every 21 davs.
First-line chemotherapy rechallenge after relapse in small cell lung cancer. Vincent M, Evans B, Smith I. Lung Unit, Royal Mars&n Hospital. Sutton. Cancer Chemother Pharmacol 1988;21:45-8. Response to second-line therapy in relapsing patients with small cell lungcarcinoma(SCLC) isoftenclaitned tobeevidenceinfavourofnoncross resistance. Fifteen patients with SCLC who had relapsed off treatment after responding to initial first-line chemotherapy were retreated with the same regimen at relapse. Ten (67%) achieved a further partial response. Median response duration was only 3 months (range 24 months), but similar poor results have been reported for most studies using second-line chemotherapy. Relapse in SCLC does not necessarily imply complete clinical resistance to first-line chemotherapy, and strict clinical criteria are required to demonstrate true non-cross resistance.
Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer. Bronchud MH, Scarffe JH, Thatcher N et al. Cancer Research Campaign Department of Medical Oncology, Paterson Institutefor Cancer Research, Manchester M20 9BX. Br J Cancer 1987;56:809-13. Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rhG-CSF) at the following dose levels: 1 ?? g, 5 ?? g, 10 ?? g, 20 ?? g and 40 ?? gkg-’ day-r for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neuuophils increased rapidly to a maximum of 100 x lOgI-’at 10 ?? gkg ’day-‘. The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the phase II part of the study thepatients weretreatedbyacombinationofintravenousadriamytin 50 mg m-*, ifosfamide 5 g m-* by i.v. infusion with mesna 8 g m20n day 1, and etoposide 120 mg m-z on days 1.2 and 3 also intravenously. The chemotherapy regime was repeated every 3 weeks. rhG-CSF was given toeachpatientfor 14daysonaltematecyclesofchemotherapyand reduced the period of absolute neutropenia considerably (median of 80%),witharetumtonormal,orabovenormal,neuuophilcountswithin 2 weeks after day 1 of chemotherapy. Six severe infective episodes were observed during the cycles of chemotherapy which did not include rhGCSF, while no infective episodes occurred when patients were treated with rhG-CSF. These results demonstrate the utility of rhG-CSF in restoring functional neutrophils to patients undergoing intensive chemotherapy.
A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung cancer. Eagan RT, Frytak S, Richardson RL et al. Division of Medical Oncology, Medical Research Statistics, Division of Thoracic Diseases, Mayo Clinic, Rochester, MN55905. J Clin Oncol 1988:6:5-8. One hundred eight eligible patients with advanced, metastatic nonsmall-cell lung cancer (NSCLC) were randomized to treatment with either cyclophosphamide, doxorubicin, andcisplatin (CAP) followed by mitomycin, lomustine, and methotrexate (MCM) on progression (sequential, 54 patients) or to CAP alternating with MCM (alternating, 54 patients). The regression rate (30%) was identical for both treatments. In addition, there were no statistically significant differences noted between treatments for regression duration (6.9 months v 7.6 months), time to progression (2.1 months v 4.4 months), or overall survival (5.5 months v 6.9 months). The lack of advantage for the theoretically superior alternating approach was probably due to a combination of relative ineffectiveness of each treatment and lack of complete noncross resistance.
Sensitivity of human non-small cell lung cancer xenografts to cyclophosphamide and cisplatin. Mattem J, Wayss K, Volm M. German Cancer Research Center, Institute of Experimental Pathology, D-6900 Heidelberg. In Vivo 1987;1:23-6. In order to establish the usefulness of the nude-mouse human tumour xenograft system as a predictive screen for antineoplastic agents, the antitumour activity of cyclophosphamide (CTX) and cisplatin (DDP), two clinically active drugs, was tested against a panel of I4 human nonsmall cell lung tumour xenografts and the experimental results were compared with the clinical results reported in the literature. The poor clinical response of non-small cell tumours was reflected in the lack of response of the xenograft tumours to these two agents.
Chemotherapy for small cell lung cancer: Induction and reinduction with voca. Stuart-Harris R, Raghavan D, Fox RM et al. Ludwiglnstitutefor Cancer Research, University of Sydney, Sydney, NSW. Aust New Zealand J Med 1987;17:279-82. Sixty-five patients with small cell lung cancer were treated with VP16, vincristinc, cyclophosphamide, and doxorubicin (VOCA) intravenously at three-week intervals. Patients with limited disease received four cycles with responders receiving radiation to the primary site and prophylactic cranial irradiation. Patients with extensive disease received chemotherapy only. Of 59 patients cvaluablc for chemotherapy rcsponsc,eight(l4%)achievedcompleteremission~d3O(5l%)partial remission. Major side-cffccts included myelosuppression, alopecia, nausea, and vomiting. Reinduction with VOCA at rclapsc yielded objective or subjective response in four of seven patients. This regimen is active in small cell lung cancer and was well tolerated by patients. Reinduction of response was possible in a small number of patients rctrcate and may provide useful palliation for those when treatment is discontinued.
Mitomycin C, vinblastine and cisplatin combination chemotherapy in the treatment of advanced non-small cell lung cancer. NomuraF,ShimokataK,SaitoH,SakaiS,WatanabeA,SakaH.Departmen1 ofMedicine. Japanese Red Cross Nagoya First Hospital, Nagoya.
s37
Cancer Chemother Pharmacol 1987;20:324-6. Thirty-one patients with previously untreated advanced non-small cell lung cancer were treated with milomycin C (10 mg/m’, day I), vinblastine (5 mg/m2, days 1 and 15), and cisplatin (80 mg/mz, day 1). Combination chemotherapy was repeated al 4-week intervals until disease progression or unacceptable toxicity. The overall response rate was 52.0%, with a median survival time of 8 months. The median duration of response was 16 weeks (range, 7-49 weeks), and 23% of the patients survived for more than 1 year. Toxicity included moderate myelosupprcssion, mild nephropathy, and severe nausea and vomiting. This combination therapy of anticancer agents appears to have antitumor activity, but not to have satisfactory therapeutic activity for advanced non-small cell lung cancer.
Retreatment
with the induction regimen in small cell lung cancer
relapsing after an initial response to short term chemotherapy.
Postmus PE, Berendsen HH. Van Zandwijk N, Splinter TAW, Burghouts JTM, Bakker W. Department of Pulmonary Diseases, State University,9713E%Groningen.EurJCancerClin0nco11987;23:1409Il. In 37 patients with small cell lung cancer treatment with five cycles of cyclophosphamide, doxorubicin and etoposide (CDE), resulted in 23 complete (CR) and 14 partial responses (PR). Median response duration was34 weeks. A~relapseallpatients weretreated withCDE.In23(62%) patients this gave a second response (6 CR, 17 PR). Factors influencing the occurrence of a second response were: 1. a CR after the first five cycles of CDE; 18 OUIof 23 CR patients responded again whereas only live of the 14 PR patients responded (P < 0.01). 2.15 out of 19 patients with a first response duration > 34 weeks reached a second response and in eight of the other 18 patients retreatment was successful (P < 0.05). Reinduction at relapse, after short term chemotherapy and a treatmentfree interval, with the induction regimen is an effective second line treatmen in paticnls with an initial CR and a first response duration of > 34 weeks.
an inactive drug in small cell lung cancer. Giaccone G. Donadio M. Bonardi G. Bagatella M. Calciati A. Division of Medical Oncology, Ospedale S. Giovanni, 10123 Torino. Eur J Cancer Clin Oncol 1987;23: 1407-g. 4’-Deoxydoxorubicin was administered to 27 evaluable patients with refractory small ccl1 lung cancer. The majority of patients had good initial performance status. One third of patients had never received doxorubicin before, and six had received a single drug alone (VM26). Myeloloxlcity waF Lllc main side-effect, and leukopenia was more pronounced than thrombocytopenia. No significant non-hematological toxicity occurred apart from skin necrosis due to drug extravasation in one cast. Two patients had partial response (7.4%; 95% confidence hmi& O-l 7.2%). The low response rate obtained in this good prognosis palicnl population dots not support further testing of this drug in small cell lung cancer.
to 7 days (I600 mg/m”). The median fall in haemoglobin (Hb) ranged from 2.2 g/l (800 mg/m2) to 3.6 @(I600 mg/m*). Nephroloxicity was encountered at all dosages and was in part, though noi entirely, dose related. 2/9 patients rccciving 800 mg/m’ and 4/6 of the patients receiving 1600 mg/m’ had a fall in glomerular f&ration rate (GFR) > 25% but < 50% 800 mg/m2 of carboplatin was well tolerated. the performance status in 9/lO (90%) courses being O-1 (ECOG scale). At 1600 mg/m2 in 6/8 (75%) courses the performance status was 2-4. There wa one lrealmcnl-related death from neutropcnia at this dose Icvel. The scverily ofnauseaand vomiting was notdose related butothertoxicillcs including diarroea, alopecia, mild ncuropathy and ototoxicity and possible CNS toxicity occured at doses of 1200 mg/m* and over. 5/7 patients with small cell lung cancer achieved a complete or partial response to lrcatmcnt. Carboplatin
or iproplatin
in advanced non-small cell lung cancer:
A cancer and leukemia group B study.
Kreisman H, Ginsberg S, Propert KJ, Richards F, Graziano S, Green M. McGill Cancer Center, The Sir Morfimer B. Davis-Jewish General 1987;71: 1049-52. Hospital,Monrreal,Que. Il3Tl.U CancerTrcatRep The effect of the cisplatin analogos carboplatin (CBIXA) or iproplalin (CHIP) was evaluated in palicnls with cxtcnsive non-small cell lung cancer. The randomized phase II design was used to achieve balance between padent groups and comparison of response rates was not a primary objective of the study. CHDCA (400 mg/m2 iv) or CHIP (270 mg/m* iv) was administered every 4 weeks until relapse of disease. Overall, 11of 70 patients (16%; 95% confidence interval: 7%-25%) responded to CBDCA and five of 71 patients (7%; 95% confidence interval: I%-13%) responded to CHIP. There were IWO complete responses to CHIP and none to CBDCA. The most frequent severe or life-thrcatcning toxic effects were thrombocytopenia and leukopcnia. Median survival for paticnls receiving CBDCA was 6.5 months; for those on CHIP it was 5.0 months (P = 0.59). CBDCA is probably active in patients with non-small cell lung cancer whereas CHIP has limited activity. Further evaluation of CBDCA as part of combination chemotherapy for non-small lung cancer is warranted.
4’-Deoxydoxorubicin,
High dose carboplatin in the treatment of lung cancer and mesothelioma: A phase I dose escalation study. Gore M.E. Calvcrt A.H. Smith I.E. The Lung Unit, Royal Marsden
Ilospilal, Surlon, Surrey. Eur J Cancer Clin Oncol 1987;23:1391-7. Sixteen paticnls with lung cancer or mcsothclioma have been treated with escalating doses of carboplatm. Five patients (10 courses) were given 800 mg/m’, four patienti (five courses) 1200 mg/m2 and seven patients (eight courses) 1600 mg/m2. Myclosuppresslon was the major toxicity cncounrcrcd. The median duration of grade 4 neutropcnia ranged from I day (XOa mg/m2) LO11days (1600 mg/mz) and the median duration of grade 4 thrombocylopcnia ranged from I day (800 mg/m2)
A phase 11 trial of chlorambucil
in non-small cell lung cancer.
Gentile PS, Woodcock TM, Blumenreich MS ctal. Division ofMedical Oncology, Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40292 Am J Clin Oncol, Cancer Clin Trials. 1987;10:515-6. A Phase II trial of high-dose chlorambucil ai 108 mg/m* was undertaken in non-small cell lung cancer. No complete or partial objective responses wcrc obscrvcd. and significant toxicily, including nausca,vomi~ing,andseizurcs,wasno~cd.Chlorambucila~thisdoscand schedulcofadministration isnotrecommended for thetreatmentofnonsmall cell lung cancer. Etoposidecombination
therapy for small cellcarcinoma ofthe lung.
Abrau RP, Willcox PA, Hewitson RH. Deparrmenr of Radiotherapy. Groote Schuw ffospital, Cape Town. Cancer Chcmother Pharmacol. 1987;20:83-84. Sixty-three conseculive patients with small cell carcinoma of the lung wcrc ucatcd by six cycles at 3-week intervals of etoposide 120 mg/m* iv. on day 1 and orally on days 2-5, adriamycin 40 mg/mz i.v. on day 1and vincristine 1.4mg/m2 i.v. on day 1. Tumour bed irradiation was adminislcrcd to patients with limited disease after chemotherapy. In limilcd-discasc and cxtcnsive-disease patients the median survival was 12 and 6 months rcspcctivcly. The 2-year survival raic (life table) in limit&disease patients was 26%. Treatment morbidity was low. A prospcctivc randomiscd Lrial is being undertaken io further evaluate Ihe role of oral ctoposidc in combination chcmothcrapy.
disease. There was partial remission, six with doxorubicin, seven with epirubicin (one death in each group), and no response in five (doxorubicin; two deaths) and seven (epirubicin; five deaths). Toxicity was greater during and after cyclophosphamide and etoposide than during and after vincristine with either doxorubicin or epirubicin. Substitution of epirubicin for doxorubicin appeared not to offer any advantage in reduction in toxicity in the treatment of small cell lung cancer as used in this series. The low complete remission rate, the relatively high proportion of non-responders and the low incidence of serious leucopenia indicates that the therapeutic regimen used was sub-optimal. It is suggested that this may bc because the treatment schedule was every four weeks instead of the more usual three-weekly treatments and the lack of cardiac toxicity may be because no patients received more than 200 mg/m2. It is concluded therefore that it would be worth including epirubicin into a more intensive treatment protocol, using a higher total dose and scheduling. the treatment every 21 davs.
First-line chemotherapy rechallenge after relapse in small cell lung cancer. Vincent M, Evans B, Smith I. Lung Unit, Royal Mars&n Hospital. Sutton. Cancer Chemother Pharmacol 1988;21:45-8. Response to second-line therapy in relapsing patients with small cell lungcarcinoma(SCLC) isoftenclaitned tobeevidenceinfavourofnoncross resistance. Fifteen patients with SCLC who had relapsed off treatment after responding to initial first-line chemotherapy were retreated with the same regimen at relapse. Ten (67%) achieved a further partial response. Median response duration was only 3 months (range 24 months), but similar poor results have been reported for most studies using second-line chemotherapy. Relapse in SCLC does not necessarily imply complete clinical resistance to first-line chemotherapy, and strict clinical criteria are required to demonstrate true non-cross resistance.
Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer. Bronchud MH, Scarffe JH, Thatcher N et al. Cancer Research Campaign Department of Medical Oncology, Paterson Institutefor Cancer Research, Manchester M20 9BX. Br J Cancer 1987;56:809-13. Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rhG-CSF) at the following dose levels: 1 ?? g, 5 ?? g, 10 ?? g, 20 ?? g and 40 ?? gkg-’ day-r for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neuuophils increased rapidly to a maximum of 100 x lOgI-’at 10 ?? gkg ’day-‘. The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the phase II part of the study thepatients weretreatedbyacombinationofintravenousadriamytin 50 mg m-*, ifosfamide 5 g m-* by i.v. infusion with mesna 8 g m20n day 1, and etoposide 120 mg m-z on days 1.2 and 3 also intravenously. The chemotherapy regime was repeated every 3 weeks. rhG-CSF was given toeachpatientfor 14daysonaltematecyclesofchemotherapyand reduced the period of absolute neutropenia considerably (median of 80%),witharetumtonormal,orabovenormal,neuuophilcountswithin 2 weeks after day 1 of chemotherapy. Six severe infective episodes were observed during the cycles of chemotherapy which did not include rhGCSF, while no infective episodes occurred when patients were treated with rhG-CSF. These results demonstrate the utility of rhG-CSF in restoring functional neutrophils to patients undergoing intensive chemotherapy.
A randomized comparative trial of sequential versus alternating cyclophosphamide, doxorubicin, and cisplatin and mitomycin, lomustine, and methotrexate in metastatic non-small-cell lung cancer. Eagan RT, Frytak S, Richardson RL et al. Division of Medical Oncology, Medical Research Statistics, Division of Thoracic Diseases, Mayo Clinic, Rochester, MN55905. J Clin Oncol 1988:6:5-8. One hundred eight eligible patients with advanced, metastatic nonsmall-cell lung cancer (NSCLC) were randomized to treatment with either cyclophosphamide, doxorubicin, andcisplatin (CAP) followed by mitomycin, lomustine, and methotrexate (MCM) on progression (sequential, 54 patients) or to CAP alternating with MCM (alternating, 54 patients). The regression rate (30%) was identical for both treatments. In addition, there were no statistically significant differences noted between treatments for regression duration (6.9 months v 7.6 months), time to progression (2.1 months v 4.4 months), or overall survival (5.5 months v 6.9 months). The lack of advantage for the theoretically superior alternating approach was probably due to a combination of relative ineffectiveness of each treatment and lack of complete noncross resistance.
Sensitivity of human non-small cell lung cancer xenografts to cyclophosphamide and cisplatin. Mattem J, Wayss K, Volm M. German Cancer Research Center, Institute of Experimental Pathology, D-6900 Heidelberg. In Vivo 1987;1:23-6. In order to establish the usefulness of the nude-mouse human tumour xenograft system as a predictive screen for antineoplastic agents, the antitumour activity of cyclophosphamide (CTX) and cisplatin (DDP), two clinically active drugs, was tested against a panel of I4 human nonsmall cell lung tumour xenografts and the experimental results were compared with the clinical results reported in the literature. The poor clinical response of non-small cell tumours was reflected in the lack of response of the xenograft tumours to these two agents.
Chemotherapy for small cell lung cancer: Induction and reinduction with voca. Stuart-Harris R, Raghavan D, Fox RM et al. Ludwiglnstitutefor Cancer Research, University of Sydney, Sydney, NSW. Aust New Zealand J Med 1987;17:279-82. Sixty-five patients with small cell lung cancer were treated with VP16, vincristinc, cyclophosphamide, and doxorubicin (VOCA) intravenously at three-week intervals. Patients with limited disease received four cycles with responders receiving radiation to the primary site and prophylactic cranial irradiation. Patients with extensive disease received chemotherapy only. Of 59 patients cvaluablc for chemotherapy rcsponsc,eight(l4%)achievedcompleteremission~d3O(5l%)partial remission. Major side-cffccts included myelosuppression, alopecia, nausea, and vomiting. Reinduction with VOCA at rclapsc yielded objective or subjective response in four of seven patients. This regimen is active in small cell lung cancer and was well tolerated by patients. Reinduction of response was possible in a small number of patients rctrcate and may provide useful palliation for those when treatment is discontinued.
Mitomycin C, vinblastine and cisplatin combination chemotherapy in the treatment of advanced non-small cell lung cancer. NomuraF,ShimokataK,SaitoH,SakaiS,WatanabeA,SakaH.Departmen1 ofMedicine. Japanese Red Cross Nagoya First Hospital, Nagoya.
s37
Cancer Chemother Pharmacol 1987;20:324-6. Thirty-one patients with previously untreated advanced non-small cell lung cancer were treated with milomycin C (10 mg/m’, day I), vinblastine (5 mg/m2, days 1 and 15), and cisplatin (80 mg/mz, day 1). Combination chemotherapy was repeated al 4-week intervals until disease progression or unacceptable toxicity. The overall response rate was 52.0%, with a median survival time of 8 months. The median duration of response was 16 weeks (range, 7-49 weeks), and 23% of the patients survived for more than 1 year. Toxicity included moderate myelosupprcssion, mild nephropathy, and severe nausea and vomiting. This combination therapy of anticancer agents appears to have antitumor activity, but not to have satisfactory therapeutic activity for advanced non-small cell lung cancer.
Retreatment
with the induction regimen in small cell lung cancer
relapsing after an initial response to short term chemotherapy.
Postmus PE, Berendsen HH. Van Zandwijk N, Splinter TAW, Burghouts JTM, Bakker W. Department of Pulmonary Diseases, State University,9713E%Groningen.EurJCancerClin0nco11987;23:1409Il. In 37 patients with small cell lung cancer treatment with five cycles of cyclophosphamide, doxorubicin and etoposide (CDE), resulted in 23 complete (CR) and 14 partial responses (PR). Median response duration was34 weeks. A~relapseallpatients weretreated withCDE.In23(62%) patients this gave a second response (6 CR, 17 PR). Factors influencing the occurrence of a second response were: 1. a CR after the first five cycles of CDE; 18 OUIof 23 CR patients responded again whereas only live of the 14 PR patients responded (P < 0.01). 2.15 out of 19 patients with a first response duration > 34 weeks reached a second response and in eight of the other 18 patients retreatment was successful (P < 0.05). Reinduction at relapse, after short term chemotherapy and a treatmentfree interval, with the induction regimen is an effective second line treatmen in paticnls with an initial CR and a first response duration of > 34 weeks.
an inactive drug in small cell lung cancer. Giaccone G. Donadio M. Bonardi G. Bagatella M. Calciati A. Division of Medical Oncology, Ospedale S. Giovanni, 10123 Torino. Eur J Cancer Clin Oncol 1987;23: 1407-g. 4’-Deoxydoxorubicin was administered to 27 evaluable patients with refractory small ccl1 lung cancer. The majority of patients had good initial performance status. One third of patients had never received doxorubicin before, and six had received a single drug alone (VM26). Myeloloxlcity waF Lllc main side-effect, and leukopenia was more pronounced than thrombocytopenia. No significant non-hematological toxicity occurred apart from skin necrosis due to drug extravasation in one cast. Two patients had partial response (7.4%; 95% confidence hmi& O-l 7.2%). The low response rate obtained in this good prognosis palicnl population dots not support further testing of this drug in small cell lung cancer.
to 7 days (I600 mg/m”). The median fall in haemoglobin (Hb) ranged from 2.2 g/l (800 mg/m2) to 3.6 @(I600 mg/m*). Nephroloxicity was encountered at all dosages and was in part, though noi entirely, dose related. 2/9 patients rccciving 800 mg/m’ and 4/6 of the patients receiving 1600 mg/m’ had a fall in glomerular f&ration rate (GFR) > 25% but < 50% 800 mg/m2 of carboplatin was well tolerated. the performance status in 9/lO (90%) courses being O-1 (ECOG scale). At 1600 mg/m2 in 6/8 (75%) courses the performance status was 2-4. There wa one lrealmcnl-related death from neutropcnia at this dose Icvel. The scverily ofnauseaand vomiting was notdose related butothertoxicillcs including diarroea, alopecia, mild ncuropathy and ototoxicity and possible CNS toxicity occured at doses of 1200 mg/m* and over. 5/7 patients with small cell lung cancer achieved a complete or partial response to lrcatmcnt. Carboplatin
or iproplatin
in advanced non-small cell lung cancer:
A cancer and leukemia group B study.
Kreisman H, Ginsberg S, Propert KJ, Richards F, Graziano S, Green M. McGill Cancer Center, The Sir Morfimer B. Davis-Jewish General 1987;71: 1049-52. Hospital,Monrreal,Que. Il3Tl.U CancerTrcatRep The effect of the cisplatin analogos carboplatin (CBIXA) or iproplalin (CHIP) was evaluated in palicnls with cxtcnsive non-small cell lung cancer. The randomized phase II design was used to achieve balance between padent groups and comparison of response rates was not a primary objective of the study. CHDCA (400 mg/m2 iv) or CHIP (270 mg/m* iv) was administered every 4 weeks until relapse of disease. Overall, 11of 70 patients (16%; 95% confidence interval: 7%-25%) responded to CBDCA and five of 71 patients (7%; 95% confidence interval: I%-13%) responded to CHIP. There were IWO complete responses to CHIP and none to CBDCA. The most frequent severe or life-thrcatcning toxic effects were thrombocytopenia and leukopcnia. Median survival for paticnls receiving CBDCA was 6.5 months; for those on CHIP it was 5.0 months (P = 0.59). CBDCA is probably active in patients with non-small cell lung cancer whereas CHIP has limited activity. Further evaluation of CBDCA as part of combination chemotherapy for non-small lung cancer is warranted.
4’-Deoxydoxorubicin,
High dose carboplatin in the treatment of lung cancer and mesothelioma: A phase I dose escalation study. Gore M.E. Calvcrt A.H. Smith I.E. The Lung Unit, Royal Marsden
Ilospilal, Surlon, Surrey. Eur J Cancer Clin Oncol 1987;23:1391-7. Sixteen paticnls with lung cancer or mcsothclioma have been treated with escalating doses of carboplatm. Five patients (10 courses) were given 800 mg/m’, four patienti (five courses) 1200 mg/m2 and seven patients (eight courses) 1600 mg/m2. Myclosuppresslon was the major toxicity cncounrcrcd. The median duration of grade 4 neutropcnia ranged from I day (XOa mg/m2) LO11days (1600 mg/mz) and the median duration of grade 4 thrombocylopcnia ranged from I day (800 mg/m2)
A phase 11 trial of chlorambucil
in non-small cell lung cancer.
Gentile PS, Woodcock TM, Blumenreich MS ctal. Division ofMedical Oncology, Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40292 Am J Clin Oncol, Cancer Clin Trials. 1987;10:515-6. A Phase II trial of high-dose chlorambucil ai 108 mg/m* was undertaken in non-small cell lung cancer. No complete or partial objective responses wcrc obscrvcd. and significant toxicily, including nausca,vomi~ing,andseizurcs,wasno~cd.Chlorambucila~thisdoscand schedulcofadministration isnotrecommended for thetreatmentofnonsmall cell lung cancer. Etoposidecombination
therapy for small cellcarcinoma ofthe lung.
Abrau RP, Willcox PA, Hewitson RH. Deparrmenr of Radiotherapy. Groote Schuw ffospital, Cape Town. Cancer Chcmother Pharmacol. 1987;20:83-84. Sixty-three conseculive patients with small cell carcinoma of the lung wcrc ucatcd by six cycles at 3-week intervals of etoposide 120 mg/m* iv. on day 1 and orally on days 2-5, adriamycin 40 mg/mz i.v. on day 1and vincristine 1.4mg/m2 i.v. on day 1. Tumour bed irradiation was adminislcrcd to patients with limited disease after chemotherapy. In limilcd-discasc and cxtcnsive-disease patients the median survival was 12 and 6 months rcspcctivcly. The 2-year survival raic (life table) in limit&disease patients was 26%. Treatment morbidity was low. A prospcctivc randomiscd Lrial is being undertaken io further evaluate Ihe role of oral ctoposidc in combination chcmothcrapy.